Glucose-Responsive Microspheres as a Smart Drug Delivery System for Controlled Release of Insulin

  • Jiaojiao Yu
  • Qiongyan Wang
  • Haofan Liu
  • Xiaosong Shan
  • Ziyan Pang
  • Pengjin Song
  • Feng Niu
  • Liandong HuEmail author
Original Research Article


Background and Objectives

Diabetes mellitus, a disease of glucose regulation, has become one of the most common medical problems in the world. At present, alternative therapy for diabetes has, to a large extent, been widely concerned with the improvement of treatment efficacy. The aims of this study were to characterize and evaluate the surface morphology of the novel glucose-responsive injectable microspheres containing insulin, along with their in vitro release and in vivo efficacy.


In this study, glucose-responsive microspheres as an emerging smart drug delivery system for controlled release of insulin were developed by an improved water-in-oil-in-water (W/O/W) double emulsion preparation method. Here, methoxypolyethylene glycol-hydrazone-4-methoxypolyethylene glycol benzoate (mPEG-Hz-mPEG4AB) was synthesized as a pH-responsive carrier.


The microspheres had a good spherical structure with a particle size of 5 ~ 10 μm. Approximately 61% of insulin was released in 15 h under a high glucose environment but was barely released within the normal glucose range in in vitro studies. After a subcutaneous injection of insulin microspheres in rats, blood glucose levels rapidly decreased within 2 h and could be maintained for 2 days in the normal range. Histopathological evaluation indicated that the microspheres were almost non-irritating.


The pH-responsive mPEG-Hz-mPEG4AB could be used as an efficient insulin microsphere carrier, and the optimized microspheres had good morphology and sustained hypoglycemic effect.


Compliance with Ethical Standards


This work was supported by the fund of the Top Young Talents Program of Hebei Province, the Scientific Research Project of Hebei Provincial High School (No. ZD2016136), the Post-graduate’s Innovation Fund Project of Hebei University (No. hbu2019ss080) and Key Research and Development Plan of Hebei Province (No. 19272701D).

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

The protocol of the study was approved by the ‘Animal Welfare and Ethical Committee of Hebei University’. The European Community guidelines as accepted principles for the use of experimental animals were adhered to.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Jiaojiao Yu
    • 1
    • 2
    • 3
  • Qiongyan Wang
    • 1
  • Haofan Liu
    • 1
  • Xiaosong Shan
    • 2
  • Ziyan Pang
    • 3
  • Pengjin Song
    • 1
  • Feng Niu
    • 4
  • Liandong Hu
    • 1
    • 2
    Email author
  1. 1.School of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Quality Control of Hebei ProvinceHebei UniversityBaodingChina
  2. 2.Affiliated Hospital of Hebei UniversityBaodingChina
  3. 3.Xingtai Third HospitalXingtaiChina
  4. 4.NBP Pharmaceutical Company Limited, CSPC Pharmaceutical Group LimitedShijiazhuangChina

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